tbuckley/cabot-search huggingface dataset:
Electronic cigarettes versus nicotine patches for smoking cessation in pregnancy: a randomized controlled trial
Authors: Peter Hajek, Dunja Przulj, Francesca Pesola, Chris Griffiths, Robert Walton, Hayden McRobbie, Tim Coleman, Sarah Lewis, Rachel Whitemore, Miranda Clark, Michael Ussher, Lesley Sinclair, Emily Seager, Sue Cooper, Linda Bauld, Felix Naughton, Peter Sasieni, Isaac Manyonda, Katie Myers Smith
Journal: Nature Medicine (2022)

Nicotine replacement therapy, in the form of nicotine patches, is commonly offered to pregnant women who smoke to help them to stop smoking, but this approach has limited efficacy in this population. Electronic cigarettes (e-cigarettes) are also used by pregnant women who smoke but their safety and efficacy in pregnancy are unknown. Here, we report the results of a randomized controlled trial in 1,140 participants comparing refillable e-cigarettes with nicotine patches. Pregnant women who smoked were randomized to e-cigarettes (n = 569) or nicotine patches (n = 571). In the unadjusted analysis of the primary outcome, validated prolonged quit rates at the end of pregnancy in the two study arms were not significantly different (6.8% versus 4.4% in the e-cigarette and patch arms, respectively; relative risk (RR) = 1.55, 95%CI: 0.95-2.53, P = 0.08). However, some participants in the nicotine patch group also used e-cigarettes during the study. In a pre-specified sensitivity analysis excluding abstinent participants who used non-allocated products, e-cigarettes were more effective than patches (6.8% versus 3.6%; RR = 1.93, 95%CI: 1.14-3.26, P = 0.02). Safety outcomes included adverse events and maternal and birth outcomes. The safety profile was found to be similar for both study products, however, low birthweight (<2,500 g) was less frequent in the e-cigarette arm (14.8% versus 9.6%; RR = 0.65, 95%CI: 0.47-0.90, P = 0.01). Other adverse events and birth outcomes were similar in the two study arms. E-cigarettes might help women who are pregnant to stop smoking, and their safety for use in pregnancy is similar to that of nicotine patches. ISRCTN62025374.
Whole blood transcriptomic profiling identifies molecular pathways related to cardiovascular mortality in heart failure
Authors: Mintu Nath, Simon P.R. Romaine, Andrea Koekemoer, Stephen Hamby, Thomas R. Webb, Christopher P. Nelson, Marcos Castellanos‐Uribe, Manolo Papakonstantinou, Stefan D. Anker, Chim C. Lang, Marco Metra, Faiez Zannad, Gerasimos Filippatos, Dirk J. van Veldhuisen, John G. Cleland, Leong L. Ng, Sean T. May, Federica Marelli‐Berg, Adriaan A. Voors, James A. Timmons, Nilesh J. Samani
Journal: European Journal of Heart Failure (2022)
Considerations For Use of Propensity Score Matching in Specific Patient Populations—Reply
Authors: Arya Zarinsefat, Amy Shui, Peter Stock
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Ultrasound triggered organic mechanoluminescence materials
Authors: Wenliang Wang, Aaron Tasset, Ilya Pyatnitskiy, Heba G. Mohamed, Rayna Taniguchi, Richard Zhou, Manini Rana, Peter Lin, Sam Lander C. Capocyan, Arjun Bellamkonda, W. Chase Sanders, Huiliang Wang
Journal: Advanced Drug Delivery Reviews (2022)
Evolving Practice Choices by Newly Certified and More Senior General Internists
Authors: Bradley M. Gray, Jonathan L. Vandergrift, Jennifer P. Stevens, Bruce E. Landon
Journal: Annals of Internal Medicine (2022)

Hospital medicine has grown as a field. However, no study has examined trends in career choices by internists over the past decade.To measure changes in practice setting for general internists.Using Medicare fee-for-service claims (2008 to 2018) and data from the American Board of Internal Medicine, practice setting types were measured annually for general internists initially certifying between 1990 and 2017.General internists (non-subspecializing) treating Medicare fee-for-service beneficiaries.Medicare fee-for-service beneficiaries aged 65 years and older with at least 20 evaluation and management (E&M) visits annually.Practice setting types were defined as hospitalist (>95% inpatient E&M), outpatient only (100% outpatient E&M), or mixed.67 902 general internists, comprising 80% of all general internists initially certified from 1990 to 2017 (n = 84 581), were studied. From 2008 to 2018, both hospitalists and outpatient-only physicians increased as percentages of general internists (25% to 40% and 23% to 38%, respectively). This was accompanied by a 56% decline in the percentage of mixed-practice physicians (52% to 23%) as these physicians largely migrated to outpatient-only practice. By 2018, 71% of newly certified general internists practiced as hospitalists compared with only 8% practicing as outpatient-only physicians. Most (86% of hospitalists in 2013) had the same practice type 5 years later. This retention rate was similar across early career and more senior physicians (86% and 85% for the 1999 and 2012 initial certification cohorts, respectively) and for the outpatient-only practice type (95%) but was only 57% for the mixed practice type.Practice setting measurement relied only on Medicare fee-for-service claims.Newly certified general internists are largely choosing hospital medicine as their career choice whereas more senior physicians increasingly see patients only in the outpatient setting.This study did not receive direct funding.
Toward Incorporating Health-Related Quality of Life as Coprimary End Points in Clinical Trials: Time to Achieve Clinical Important Differences and QoL Profiles
Authors: Val Gebski, Andreas Obermair, Monika Janda
Journal: Journal of Clinical Oncology (2022)

PURPOSE Besides morbidity and mortality, quality of life (QoL) is a key outcome of cancer treatments. Trials on the basis of clinical outcomes have expectations that QoL outcomes can be either tolerated or improved. Simultaneously considering QoL and clinical outcomes is challenging with lack of suitable metrics allowing incorporation of QoL as coprimary end points in clinical trial design and utilization of hierarchical hypothesis testing. METHOD We propose combining time to achieving a minimal clinically important difference (MCID) and probabilities of a MCID occurring in each QoL domain to provide QoL metrics analogous to those used for clinical end points. For QoL domains of interest, these yield QoL profiles, time to MCID, and number needed to treat. Incorporation of QoL as coprimary end points in clinical trial designs through hierarchical hypothesis testing can easily be achieved. The noninferiority designed Laparoscopic Approach to Carcinoma of the Endometrium trial, evaluating laparoscopic versus open abdominal surgery for endometrial cancer with Functional Assessment of Cancer Therapy–General QoL domains, is used to illustrate the usefulness of these metrics. RESULTS This analysis revealed that laparoscopic surgery had a significant shorter time to MCID for physical and functional well-being QoL domains (physical mean: 1.5 months, 95% CI, 0.5 to 2.6; P = .002; and functional mean: 1.4 months; 95% CI, 0.4 to 2.4; P = .003) than abdominal surgery, but little difference between the two approaches for psychologic social and emotion well-being. Probability profile plots show a consistent &gt; 2-fold higher chance of attaining a MCID for physical and functional well-being over time for laparoscopic compared with abdominal surgery. CONCLUSION This analysis reinforces the potential value of novel MCID metrics and their usefulness in raising the profile of QoL outcomes to complement clinical end points. The methods will allow health professionals to counsel patients about QoL outcomes and clinical outcomes simultaneously.
Post-transplant cyclophosphamide alters immune signatures and leads to impaired T cell reconstitution in allogeneic hematopoietic stem cell transplant
Authors: Chenchen Zhao, Matthew Bartock, Bei Jia, Neal Shah, David F. Claxton, Baldeep Wirk, Kevin L. Rakszawski, Myles S. Nickolich, Seema G. Naik, Witold B. Rybka, W Christopher C. Ehmann, Raymond J. Hohl, Jessica Valentin, Michelle Bernas-Peterson, Emily M. Gerber, Michele Zimmerman, Joseph A. Mierski, Shin Mineishi, Hong Zheng
Journal: Journal of Hematology & Oncology (2022)

Abstract Despite the increased usage of post-transplant cyclophosphamide (PTCy) in allogeneic hematopoietic stem cell transplantation (allo-HSCT), our knowledge of immune reconstitution post-allo-HSCT in the setting of PTCy is limited. Adequate immune reconstitution is the key to a successful transplant. In this study, we aim to investigate the effect of PTCy on the reconstitution of each immune component; more focus was placed on the immunophenotype and functions of T cells. Using blood samples from patients who underwent allo-HSCT under regimens containing PTCy ( n = 23) versus those who received no PTCy ( n = 14), we examined the impact of PTCy on the post-transplant immune response. We demonstrated a distinct T cell immune signature between PTCy versus non-PTCy group. PTCy significantly delayed T cell reconstitution and affected the T cell subsets by increasing regulatory T cells (Treg) while reducing naïve T cells. In addition, we observed remarkable enhancement of multiple inhibitory receptors (TIGIT, PD-1, TIM-3, CD38, CD39) on both CD4 + and CD8 + T cells on day 30 post-transplantation in patients who received PTCy. Importantly, upregulation of PD-1 on CD8 T cells was persistent through day 180 and these T cells were less functional, manifested by reduced cytokine production upon anti-CD3/CD28 stimulation. Furthermore, we found a significant correlation of T cell immune phenotypes to clinical outcome (disease relapse and GVHD) in patients who received PTCy. Our novel findings provide critical information to understand the mechanism of how PTCy impacts immune reconstitution in allo-HSCT and may subsequently lead to optimization of our clinical practice using this treatment.
Abstract IA024: The role of the epigenome and phenotypic plasticity in colorectal cancer evolution
Authors: Trevor A. Graham
Journal: Cancer Research (2022)

Abstract The evolutionary dynamics of colorectal metastasis and the role of the epigenome in disease progression remain to be fully determined. We have used multi-region, multi-omic profiling (DNA, RNA and chromatin), together with computational modelling, of a prospectively collected cohort of primary CRCs (pCRCs) and DNA and RNA analysis of a retrospective series of metastatic CRCs (mCRCs) to define pCRC biology and track clonal evolution from primary tumour to metastasis. Computational analysis of multi-region sequencing data provided a sensitive test confirming subclonal selection is rare in pCRCs. We detected substantial epigenetic rewiring at the outset of pCRC formation, implicating changes in chromatin accessibility in the initial genesis of CRCs. Using DNA to trace clonal ancestry and overlaying RNA to measure gene expression phenotypes, we observe widespread gene expression changes without underlying clonal selection, indicative that pCRC cells are phenotypically plastic. In mCRCs, we observe that the karyotype of the primary tumour is often not substantially modified in metastasis, across multiple organs, through treatment and over substantial periods of time. This is suggestive that stabilising selection, acting on copy number alterations, constrains karyotype evolution. Paired analysis of DNA and RNA in metastasis indicate that the phenotypic plasticity persists during metastatic spread. Epigenetic rewiring and phenotypic plasticity play potentially causative roles in the genesis and progression of colorectal cancer. Citation Format: Trevor A. Graham. The role of the epigenome and phenotypic plasticity in colorectal cancer evolution [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr IA024.
Initial Phase I Safety Study of Gedatolisib plus Cofetuzumab Pelidotin for Patients with Metastatic Triple-Negative Breast Cancer
Authors: Milan Radovich, Jeffrey P. Solzak, Chao J. Wang, Bradley A. Hancock, Sunil Badve, Sandra K. Althouse, Steven M. Bray, Anna Maria V. Storniolo, Tarah J. Ballinger, Bryan P. Schneider, Kathy D. Miller
Journal: Clinical Cancer Research (2022)

The PI3K pathway is dysregulated in the majority of triple-negative breast cancers (TNBC), yet single-agent inhibition of PI3K has been ineffective in TNBC. PI3K inhibition leads to an immediate compensatory upregulation of the Wnt pathway. Dual targeting of both pathways is highly synergistic against TNBC models in vitro and in vivo. We initiated a phase I clinical trial combining gedatolisib, a pan-class I isoform PI3K/mTOR inhibitor, and cofetuzumab pelidotin, an antibody-drug conjugate against the cell-surface PTK7 protein (Wnt pathway coreceptor) with an auristatin payload.Participants (pt) had metastatic TNBC or estrogen receptor (ER) low (ER and PgR < 5%, HER2-negative) breast cancer, and had received at least one prior chemotherapy for advanced disease. The primary objective was safety. Secondary endpoints included overall response rate (ORR), clinical benefit at 18 weeks (CB18), progression-free survival (PFS), and correlative analyses.A total of 18 pts were enrolled in three dose cohorts: gedatolisib 110 mg weekly + cofetuzumab pelidotin 1.4 mg/kg every 3 weeks (n = 4), 180 mg + 1.4 mg/kg (n = 3), and 180 mg + 2.8 mg/kg (n = 11). Nausea, anorexia, fatigue, and mucositis were common but rarely reached ≥grade 3 severity. Myelosuppression was uncommon. ORR was 16.7% (3/18). An additional 3 pts had stable disease (of these 2 had stable disease for >18 weeks); CB18 was 27.8%. Median PFS was 2.0 months (95% confidence interval for PFS: 1.2-6.2). Pts with clinical benefit were enriched with genomic alterations in the PI3K and PTK7 pathways.The combination of gedatolisib + cofetuzumab pelidotin was well tolerated and demonstrated promising clinical activity. Further investigation of this drug combination in metastatic TNBC is warranted.
Abstract B007: Design and construction of evolutionary-guided "selection gene drive" therapy
Authors: Scott M. Leighow, Haider Inam, Justin R. Pritchard
Journal: Cancer Research (2022)

Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Proffered Abstracts section (PR014) of the Conference Proceedings. Citation Format: Scott M. Leighow, Haider Inam, Justin R. Pritchard. Design and construction of evolutionary-guided "selection gene drive" therapy [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr B007.
NIR‐II J‐Aggregated Pt(II)‐Porphyrin‐Based Phosphorescent Probe for Tumor‐Hypoxia Imaging
Authors: Wansu Zhang, Shangyu Chen, Pengfei Sun, Shuai Ye, Quli Fan, Jun Song, Pengju Zeng, Junle Qu, Wai‐Yeung Wong
Journal: Advanced Healthcare Materials (2022)

Abstract The luminescence of traditional phosphorescence‐based hypoxia probes is limited to the visible and first near‐infrared wavelength regions (&lt;1000 nm), which has defects of higher light scattering and lower penetration depth in contrast with the second near‐infrared wavelength window (NIR‐II, 1000–1700 nm) for optical bioimaging. Herein, 5,15‐bis(2,6‐bis(dodecyloxy)phenyl)‐porphyrin platinum(II) (PpyPt) with J‐aggregation induced NIR‐II phosphorescence is reported. J‐aggregates of PpyPt are confirmed by the X‐ray diffraction data in the crystalline state. Moreover, the emission and excitation spectra of PpyPt in the solid states reveal NIR‐II luminescence feature of PpyPt in J‐aggregates. More importantly, by preparation of water‐soluble PpyPt nanoparticles (PpyPt NPs 4.76 ) with J‐aggregates, it has NIR‐II phosphorescent lifetime of microseconds and good oxygen‐sensitivity in water. Moreover, the good biological hypoxia‐sensing potential of PpyPt NPs 4.76 is demonstrated in cells and 4T1‐tumor‐bearing mice. This study provides an efficient strategy to design NIR‐II phosphorescent probe for sensitive tumor‐hypoxia detection through the construction of J‐aggregates.
ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm disrupt IFN therapeutic efficacy during coronavirus infection
Authors: Rajendra Karki, SangJoon Lee, Raghvendra Mall, Nagakannan Pandian, Yaqiu Wang, Bhesh Raj Sharma, RK Subbarao Malireddi, Dong Yang, Sanja Trifkovic, Jacob A. Steele, Jon P. Connelly, Gella Vishwanath, Mitnala Sasikala, Duvvur Nageshwar Reddy, Peter Vogel, Shondra M. Pruett-Miller, Richard Webby, Colleen Beth Jonsson, Thirumala-Devi Kanneganti
Journal: Science Immunology (2022)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), continues to cause substantial morbidity and mortality in the ongoing global pandemic. Understanding the fundamental mechanisms that govern innate immune and inflammatory responses during SARS-CoV-2 infection is critical for developing effective therapeutic strategies. Whereas interferon (IFN)–based therapies are generally expected to be beneficial during viral infection, clinical trials in COVID-19 have shown limited efficacy and potential detrimental effects of IFN treatment during SARS-CoV-2 infection. However, the underlying mechanisms responsible for this failure remain unknown. In this study, we found that IFN induced Z-DNA-binding protein 1 (ZBP1)–mediated inflammatory cell death, PANoptosis, in human and murine macrophages and in the lungs of mice infected with β-coronaviruses, including SARS-CoV-2 and mouse hepatitis virus (MHV). In patients with COVID-19, expression of the innate immune sensor ZBP1 was increased in immune cells from those who succumbed to the disease compared with those who recovered, further suggesting a link between ZBP1 and pathology. In mice, IFN-β treatment after β-coronavirus infection increased lethality, and genetic deletion of Zbp1 or its Zα domain suppressed cell death and protected the mice from IFN-mediated lethality during β-coronavirus infection. Overall, our results identify that ZBP1 induced during coronavirus infection limits the efficacy of IFN therapy by driving inflammatory cell death and lethality. Therefore, inhibiting ZBP1 activity may improve the efficacy of IFN therapy, paving the way for the development of new and critically needed therapeutics for COVID-19 as well as other infections and inflammatory conditions where IFN-mediated cell death and pathology occur.
Use of dexmedetomidine for sedation in mechanically ventilated adult ICU patients: a rapid practice guideline
Authors: Morten H. Møller, Waleed Alhazzani, Kimberley Lewis, Emilie Belley-Cote, Anders Granholm, John Centofanti, William B. McIntyre, Jessica Spence, Zainab Al Duhailib, Dale M. Needham, Laura Evans, Annika Reintam Blaser, Margaret A. Pisani, Frederick D’Aragon, Manu Shankar-Hari, Mohammed Alshahrani, Giuseppe Citerio, Rakesh C. Arora, Sangeeta Mehta, Timothy D. Girard, Otavio T. Ranzani, Naomi Hammond, John W. Devlin, Yahya Shehabi, Pratik Pandharipande, Marlies Ostermann
Journal: Intensive Care Medicine (2022)
Hospitalised patients with breakthrough COVID-19 following vaccination during two distinct waves in Israel, January to August 2021: a multicentre comparative cohort study
Authors: Tal Brosh-Nissimov, Yasmin Maor, Meital Elbaz, Shelly Lipman-Arens, Yonit Wiener-Well, Khetam Hussein, Efrat Orenbuch-Harroch, Regev Cohen, Oren Zimhony, Bibiana Chazan, Lior Nesher, Galia Rahav, Hiba Zayyad, Mirit Hershman-Sarafov, Miriam Weinberger, Ronza Najjar-Debbiny, Michal Chowers
Journal: Eurosurveillance (2022)

Background Changing patterns of vaccine breakthrough can clarify vaccine effectiveness. Aim To compare breakthrough infections during a SARS-CoV-2 Delta wave vs unvaccinated inpatients, and an earlier Alpha wave. Methods In an observational multicentre cohort study in Israel, hospitalised COVID-19 patients were divided into three cohorts: breakthrough infections in Comirnaty-vaccinated patients (VD; Jun–Aug 2021) and unvaccinated cases during the Delta wave (ND) and breakthrough infections during an earlier Alpha wave (VA; Jan–Apr 2021). Primary outcome was death or ventilation. Results We included 343 VD, 162 ND and 172 VA patients. VD were more likely older (OR: 1.06; 95% CI: 1.05–1.08), men (OR: 1.6; 95% CI: 1.0–2.5) and immunosuppressed (OR: 2.5; 95% CI: 1.1–5.5) vs ND. Median time between second vaccine dose and admission was 179 days (IQR: 166–187) in VD vs 41 days (IQR: 28–57.5) in VA. VD patients were less likely to be men (OR: 0.6; 95% CI: 0.4–0.9), immunosuppressed (OR: 0.3; 95% CI: 0.2–0.5) or have congestive heart failure (OR: 0.6; 95% CI: 0.3–0.9) vs VA. The outcome was similar between all cohorts and affected by age and immunosuppression and not by vaccination, variant or time from vaccination. Conclusions Vaccination was protective during the Delta variant wave, as suggested by older age and greater immunosuppression in vaccinated breakthrough vs unvaccinated inpatients. Nevertheless, compared with an earlier post-vaccination period, breakthrough infections 6 months post-vaccination occurred in healthier patients. Thus, waning immunity increased vulnerability during the Delta wave, which suggests boosters as a countermeasure.